Early increase in left ventricular compliance after myocardial infarction.

The left ventricular (LV) pressure-volume (P-V) relationship is a resultant of several determinants, including initial ventricular volume, geometry, and wall stiffness. A quantitative index of one of these determinants, LV wall stiffness, was developed from a mathematical analysis of the isolated P-V relationship. Since this relationship was exponential, stiffness (dP/dV) could be expressed by the equation dP/dV = aP + b, where a and b are constants. The a constant, termed the passive elastic modulus, was independent of both pressure and volume, was modified only slightly by changes in geometry, and thus was primarily affected by changes in wall stiffness. LV wall stiffness was assessed by determination of the passive elastic modulus in eight normal canine hearts and in five hearts 1 hr after acute myocardial infarction. The value of the passive elastic modulus for the normal canine LV was found to be 0.099+/-0.006 cc(-1). In the five infarcted hearts there was a modest, but statistically insignificant, shift of the P-V curves from control, such that for the same pressure the infarcted hearts contained greater volume. However, the passive elastic modulus decreased 41% to 0.057+/-0.006 cc(-1) (P < 0.001). Thus, although LV wall stiffness may increase later in the course of myocardial infarction, it is concluded that it was significantly decreased 1 hr after infarction. Calculation of the passive elastic modulus provided a sensitive means of detecting such changes, whereas P-V curves alone were generally insensitive.

Application of conditional probability analysis to the clinical diagnosis of coronary artery disease.

Analysis of multiple noninvasive tests offers the promise of more accurate diagnosis of coronary artery disease, but discordant test responses can occur frequently and, when observed, result in diagnostic uncertainty. Accordingly, 43 patients undergoing diagnostic coronary angiography were evaluated by noninvasive testing and the results subjected to analysis using Bayes' theorem of conditional probability. The procedures used included electrocardiographic stress testing for detection of exercise-induced ST segment depression, cardiokymographic stress testing for detection of exercise-induced precordial dyskinesis, myocardial perfusion scintigraphy for detection of exercise-induced relative regional hypoperfusion, and cardiac fluoroscopy for detection of coronary artery calcification. The probability for coronary artery disease was estimated by Bayes' theorem from each patient's age, sex, and symptom classification, and from the observed test responses. This analysis revealed a significant linear correlation between the predicted probability for coronary artery disease and the observed prevalence of angiographic disease over the entire range of probability from 0 to 100% (P less than 0.001 by linear regression). The 12 patients without angiographic disease had a mean posttest likelihood of only 7.0 +/- 2.6% despite the fact that 13 of the 60 historical and test responses were falsely "positive." In contrast, the mean posttest likelihood was 94.1 +/- 2.8% in the 31 patients with angiographic coronary artery disease, although 45 of the 155 historical and test responses were falsely "negative." In 8 of the 12 normal patients, the final posttest likelihood was under 10% and in 26 of the 31 coronary artery disease patients, it was over 90%. These estimates also correlated well with the pooled clinical judgment of five experienced cardiologists (P less than 0.001 by linear regression). The observed change in probability for disease for each of the 15 different test combinations correlated with their information content predicted according to Shannon's theorem (P less than 0.001 by linear regression). These results support the use of probability analysis in the clinical diagnosis of coronary artery disease and provide a formal basis for comparing the relative diagnostic effectiveness and cost-effectiveness of different test combinations.

Regulation of insulin-like growth factor-I and its receptor in rat aorta after balloon denudation. Evidence for local bioactivity.

Local production of growth factors may play a major role in vascular repair after injury. We examined the regulation of insulin-like growth factor-I (IGF-I) and its specific membrane receptor in balloon-denuded rat aorta. Aortic IGF-I mRNA and radioimmunoassayable IGF-I content increased severalfold after balloon denudation with a peak at 7 d after injury. This coincided with a reciprocal 25% decrease in IGF-I receptor mRNA content and a 40% decrease in total 125I-IGF-I binding. Scatchard analysis indicated a single class of binding sites, with a decrease in receptor number at 7 d compared to control and no change in affinity. By in situ hybridization the predominant site of IGF-I expression in the normal and the denuded vessel wall was the medial smooth muscle cell. After denudation there was a relative decrease in IGF-I receptor mRNA in the medial cells as compared to the neointima, suggesting that the site of IGF-I action was predominantly in the medial layer. These data suggest that local expression and action of IGF-I are significant in the promotion of smooth muscle cell proliferation after arterial injury.

Abundant expression of parathyroid hormone-related protein in primary rat aortic smooth muscle cells accompanies serum-induced proliferation.

Parathyroid hormone-related protein (PTHrP), which is responsible for producing hypercalcemia in patients with humoral hypercalcemia of malignancy, has recently been identified in several normal tissues. Because PTHrP, like parathyroid hormone (PTH), is known to exhibit vasodilatory properties, we investigated the expression and regulation of PTHrP mRNA in cultured rat aortic smooth muscle cells (SMC). We report here that PTHrP mRNA is expressed in SMC and is markedly induced by serum in a time- and concentration-dependent fashion. Addition of 10% fetal calf serum to serum-deprived, confluent cells, resulted in a marked induction of PTHrP mRNA by 2 h with a peak at 4-6 h. PTHrP was detected in SMC by immunocytochemistry and radioimmunoassay of conditioned medium, and was shown to be up-regulated within 24 h after the addition of serum. The serum induction of PTHrP mRNA was blocked by actinomycin D and by cycloheximide indicating the need for protein synthesis to evoke the serum effect on PTHrP gene transcription. In addition, treatment with dexamethasone, which has been previously shown to reduce the constitutive expression of PTHrP in human cancer cells, also blunted the serum induction of PTHrP mRNA in SMC. Treatment of quiescent cells with the serum mitogens platelet-derived growth factor or insulin-like growth factor-I had no effect on PTHrP, whereas the vasoactive peptides endothelin, norepinephrine and thrombin stimulated PTHrP expression. Exogenous addition of recombinant PTHrP-(1-141) had no significant effect on SMC DNA synthesis as measured by [3H]thymidine incorporation. In summary, the abundance of PTHrP mRNA and the characteristics of its regulation in SMC suggest a major role for PTHrP as a local modulator in vascular smooth muscle.

Coronary heart disease. Differential hemodynamic, metabolic, and electrocardiographic effects in subjects with and without angina pectoris during atrial pacing.

Right atrial pacing was performed in 41 subjects with coronary heart disease. Twenty developed angina pectoris during pacing, while 21 did not. The extent of coronary artery disease, as judged by selective cinearteriography, was similar in the two groups. Both had significant increases in heart rate and pressure-time per minute, but there was no significant difference in either of these parameters between groups. Among the hemodynamic parameters measured, the only statistically significant change was in the cardiac index which fell slightly but significantly in the angina group. There were no differences in myocardial oxygen extraction either within each group or between groups. In the angina group, however, 14 of 20 subjects exhibited abnormal myocardial lactate metabolism during pacing. The mean change was highly significant (P < 0.01). In the nonangina group, eight of 21 subjects had abnormal lactate metabolism during pacing and the mean change was significant (P < 0.05). There was no correlation between abnormal lactate metabolism and electrocardiographic evidence of myocardial ischemia in either group. Sublingual nitroglycerin, given to five subjects with angina while pacing was continued, resulted in prompt relief of symptoms, but abnormal lactate metabolism and ST-segment depression were unaffected after 10 min. By contrast, when anginal symptoms were relieved in five subjects by cessation of pacing, symptomatic improvement was accompanied by marked improvement in lactate metabolism after 10 min. Although angina pectoris appears to be related statistically to subnormal left ventricular function and abnormal lactate metabolism, there is significant individual variation.

Long-term effects on clinical outcomes of aggressive lowering of low-density lipoprotein cholesterol levels and low-dose anticoagulation in the post coronary artery bypass graft trial. Post CABG Investigators.

BACKGROUND: The Post Coronary Artery Bypass Graft Trial, designed to compare the effects of 2 lipid-lowering regimens and low-dose anticoagulation versus placebo on progression of atherosclerosis in saphenous vein grafts of patients who had had CABG surgery, demonstrated that aggressive lowering of LDL cholesterol (LDL-C) levels to <100 mg/dL compared with a moderate reduction to 132 to 136 mg/dL decreased the progression of atherosclerosis in grafts. Low-dose anticoagulation did not significantly affect progression. METHODS AND RESULTS: Approximately 3 years after the last trial visit, Clinical Center Coordinators contacted each patient by telephone to ascertain the occurrence of cardiovascular events and procedures. The National Death Index was used to ascertain vital status for patients who could not be contacted. Vital status was established for all but 3 of 1351 patients. Information on nonfatal events was available for 95% of surviving patients. A 30% reduction in revascularization procedures and 24% reduction in a composite clinical end point were observed in patients assigned to aggressive strategy compared with patients assigned to moderate strategy during 7.5 years of follow-up, P=0. 0006 and 0.001, respectively. Reductions of 35% in deaths and 31% in deaths or myocardial infarctions with low-dose anticoagulation compared with placebo were also observed, P=0.008 and 0.003, respectively. CONCLUSIONS: -The long-term clinical benefit observed during extended follow-up in patients assigned to the aggressive strategy is consistent with the angiographic findings of delayed atherosclerosis progression in grafts observed during the trial. The apparent long-term benefit of low-dose warfarin remains unexplained.

Aggressive cholesterol lowering delays saphenous vein graft atherosclerosis in women, the elderly, and patients with associated risk factors. NHLBI post coronary artery bypass graft clinical trial. Post CABG Trial Investigators.

BACKGROUND: The NHLBI Post Coronary Artery Bypass Graft trial (Post CABG) showed that aggressive compared with moderate lowering of low-density lipoprotein-cholesterol (LDL-C) decreased obstructive changes in saphenous vein grafts (SVGs) by 31%.1 Using lovastatin and cholestyramine when necessary, the annually determined mean LDL-C level ranged from 93 to 97 mg/dL in aggressively treated patients and from 132 to 136 mg/dL in the others (P<0.001). METHODS AND RESULTS: The present study evaluated the treatment effect in subgroups defined by age, gender, and selected coronary heart disease (CHD) risk factors, ie, smoking, hypertension, diabetes mellitus, high-density lipoprotein cholesterol (HDL-C) <35 mg/dL, and triglyceride serum levels >/=200 mg/dL at baseline. As evidenced by similar odds ratio estimates of progression (lumen diameter decrease >/=0.6 mm) and lack of interactions with treatment, a similar beneficial effect of aggressive lowering was observed in elderly and young patients, in women and men, in patients with and without smoking, hypertension, or diabetes mellitus, and those with and without borderline high-risk triglyceride serum levels. The change in minimum lumen diameter was in the same direction for all subgroup categories, without significant interactions with treatment. CONCLUSIONS: Aggressive LDL-C lowering delays progression of atherosclerosis in SVGs irrespective of gender, age, and certain risk factors for CHD.

Effect of an aggressive lipid-lowering strategy on progression of atherosclerosis in the left main coronary artery from patients in the post coronary artery bypass graft trial.

BACKGROUND: The Post Coronary Artery Bypass Graft Trial, designed to compare the effects of two lipid-lowering regimens and low-dose anticoagulation versus placebo on progression of atherosclerosis in saphenous vein grafts of patients who had had CABG surgery, demonstrated that aggressive lowering of LDL cholesterol levels to a mean yearly cholesterol level from 93 to 97 mg/dL compared with a moderate reduction to a level of 132 to 136 mg/dL decreased the progression of atherosclerosis in saphenous vein grafts. Low-dose anticoagulation did not affect progression. This secondary analysis tested the hypothesis that a similar decrease in progression of atherosclerosis would also be present in native coronary arteries as measured in the left main coronary artery (LMCA). METHODS AND RESULTS: A sample of 402 patients was randomly selected from 1102 patients who had baseline and follow-up views of the LMCA suitable for analysis. Patients treated with the aggressive lipid-lowering strategy had less progression of atherosclerosis in the LMCA as measured by changes in minimum (P=0.0003) lumen diameter or the maximum percent stenosis (P=0.001), or the presence of substantial progression (P=0.008), or vascular occlusion (P=0.005) when compared with the moderate strategy. CONCLUSIONS: A strategy of aggressive lipid lowering results in significantly less atherosclerosis progression than a moderate approach in LMCAs.

The aggressive low density lipoprotein lowering controversy.

Recent clinical trials have provided unequivocal evidence of major cardiovascular benefits from low density lipoprotein (LDL) lowering with statins. However, the three critical unresolved questions about aggressive LDL lowering are the shape of the curve relating cardiac events to LDL, the best surrogate measurement for assessing therapeutic efficacy and the best target for LDL therapy. The relation between cardiac events and LDL is curvilinear, both epidemiologically and during therapy. The benefit of lipid lowering diminishes progressively and becomes difficult to detect at lower LDL levels without a very large sample size. Assessment of the benefits of lipid lowering is further confounded by differences in the level of pretreatment LDL and by the non-LDL lowering effects of statins. Both epidemiologic studies and large randomized clinical trials have produced conflicting results concerning the best LDL target. Failure to reduce the event rate in patients with pretreatment LDL <125 mg (Cholesterol And Recurrent Events [CARE] trial) alerts us to the risk of extrapolating epidemiologic data to clinical practice, yet subset analysis of some clinical trials suggests the greatest benefit appears in those patients with the lowest on-treatment LDL levels (Scandinavian Simvastatin Survival Study [4S]). This controversy should be resolved in the next few years by several important on-going trials. In the face of seemingly contradictory data from current clinical trials, we can only speculate that very aggressive LDL lowering to <80 mg/dl could be accompanied by a modest therapeutic benefit beyond the current recommendations of the National Cholesterol Education Program. If any benefit is observed, it will have to be balanced against a small potential for increased adverse events.

Percutaneous excimer laser angioplasty of aortocoronary saphenous vein grafts.

Percutaneous coronary excimer laser angioplasty was successfully performed in two patients. An 85 year old woman with a 99% stenosis in a vein graft to a posterior descending artery had the stenosis reduced to 30% with laser angioplasty. Subsequent balloon angioplasty reduced the stenosis further to 20%. A second patient, a man aged 50 years, had multiple previous balloon angioplasties and stent implantation with two subsequent percutaneous atherectomies. Laser angioplasty of the vein graft to the obtuse marginal branch reduced the first of three sequential lesions from 60% to 40%, the second lesion from 90% to none and the third from 60% to 20% without the need for balloon angioplasty. Both procedures were well tolerated without chest pain, burning, vascular perforation or thrombus formation. These cases demonstrate the feasibility of safely performing percutaneous coronary excimer laser angioplasty. Additional studies are indicated to determine the clinical role and potential benefits of this procedure in relation to established procedures and other experimental devices.

A paradigm for restenosis based on cell biology: clues for the development of new preventive therapies.

Angioplasty causes substantial injury to the coronary artery intima and media that is unrecognizable by angiography. On the basis of a substantial body of research in oncology and wound healing, it is hypothesized that restenosis is a manifestation of the general wound healing response expressed specifically in vascular tissue. The temporal response to injury occurs in three characteristic phases: inflammation, granulation and extracellular matrix remodeling. The specific expression of these phases in the coronary artery leads to intimal hyperplasia at 1 to 4 months. The major milestones in the temporal sequence of restenosis are platelet aggregation, inflammatory cell infiltration, release of growth factors, medial smooth muscle cell modulation and proliferation, proteoglycan deposition and extracellular matrix remodeling. Each step has potential inhibitors that could be used for preventive therapy. Resolution of restenosis, however, probably requires both creation of the largest possible residual lumen and substantial inhibition of intimal hyperplasia.

Myocardial contractile reserve on dobutamine echocardiography predicts late spontaneous improvement in cardiac function in patients with recent onset idiopathic dilated cardiomyopathy.

OBJECTIVES: The purpose of this study was to determine whether identification of contractile reserve with dobutamine would predict recovery of myocardial function during follow-up in patients with recent onset idiopathic dilated cardiomyopathy (IDC). BACKGROUND: The prognosis of patients presenting with new onset IDC is variable and difficult to predict. METHODS: Twenty-two patients (17 men, 5 women, 46 +/- 14 years) with recently diagnosed IDC (4 +/- 3 months) underwent dobutamine echocardiography. Left ventricular ejection fraction (LVEF) and LV sphericity before and at peak dobutamine infusion (30 +/- 11 microg/kg/min) were determined. A follow-up echocardiographic assessment was done at 6 +/- 4 months. RESULTS: The LVEF on dobutamine was directly related to baseline LV mass expressed as g/ml (Pearson r = 0.65, p = 0.0003). Baseline variables that were significantly predictive of follow-up LVEF were deceleration time (r = 0.69, p = 0.0006), wall motion score index (WMSI) (r = -0.63, p = 0.002), LV mass (r = 0.56, p = 0.008) and LVEF on dobutamine (r = 0.84, p = 0.0001). When either deceleration time or WMSI or LV mass was entered into a regression equation to predict follow-up LVEF, the LVEF on dobutamine added significantly to predictive power. However, if LVEF on dobutamine was entered first, none of the other three variables added significantly to prediction. Baseline LV sphericity at end diastole (ED) (r = 0.13, p = 0.6) did not correlate with follow-up LV sphericity in ED, whereas LV sphericity in ED on dobutamine (ED [r = 0.70, p = 0.0004]) correlated with LV sphericity in ED on follow up. CONCLUSIONS: This study demonstrates that dobutamine-induced improvement in baseline LVEF and LV sphericity identifies patients with IDC who exhibit substantial improvement in LV function and geometry over time.

Comprehensive noninvasive evaluation of left atrial myxomas using cardiac cine-computed tomography.

This report describes the first clinical experience with ultrafast (cine) computed tomography for evaluating intracardiac masses. Two patients had a left atrial myxoma that was comprehensively described (size, location, site of attachment and relation to the mitral valve) preoperatively by cine-computed tomography. The information content of the studies exceeded that of two-dimensional echocardiography, and both patients were operated on without invasive cardiac catheterization. This early experience with a new minimally invasive high temporal and spatial resolution technology suggests that cine-computed tomography may be uniquely suited for precise evaluation of intraatrial masses.

Computer-assisted diagnosis in the noninvasive evaluation of patients with suspected coronary artery disease.

A microcomputer program called CADENZA, which employs Bayes' theorem to analyze and report the results of various clinical descriptors and noninvasive tests relative to the diagnosis of coronary artery disease, was evaluated in 1,097 consecutive patients without previous myocardial infarction. With this program, each patient was characterized by a probability for coronary artery disease, based on Framingham risk factor analysis, symptom characterization, electrocardiographic stress testing, cardiokymography, cardiac fluoroscopy, thallium perfusion scintigraphy and technetium equilibrium-gated blood pool scintigraphy. A total of 11,808 probability estimates derived from various combinations of the available observations were analyzed: 2,180 in 170 patients undergoing coronary angiography and 9,628 in 969 patients who completed a 1 year follow-up for coronary events. The predicted probability of disease correlated linearly with observed angiographic prevalence in the 170 patients who subsequently had coronary angiography (prevalence = [0.001 +/- 0.011] + [0.966 +/- 0.019] X probability). The difference between probability and prevalence averaged 3.1%, and the magnitude of this correlation was not affected by the type or amount of data analyzed. The prevalence of multivessel disease in these patients increased as a monotonic function of disease probability. Below a probability of 25%, single vessel disease was slightly more common than multivessel disease. Above a probability of 75%, multivessel disease predominated. In the 969 patients followed up for 1 year from the date of testing, the incidence of cardiac death and nonfatal infarction increased as a cubic function of disease probability (from approximately 0 to 8% per year for each). Above a probability of 90%, however, the standard deviation for predicting these events was wide. These data indicate that Bayes' theorem in general--and CADENZA in particular--is an accurate, clinically applicable means for quantifying the prevalence of angiographic coronary artery disease, the risk of multivessel disease and the incidence of morbid coronary events in the year after testing.

Implantation and recovery of temporary metallic stents in canine coronary arteries.

OBJECTIVES: The purpose of this study was to test the feasibility of implanting and retrieving a heat-activated recoverable temporary stent and to determine its effect on the angiographic, gross and histologic appearance of a normal coronary artery wall. BACKGROUND: Permanent coronary stenting is associated with a significant incidence of thrombosis, bleeding and vascular complications. These may be avoided by temporarily stenting for a period of hours to several days. METHODS: Seventy-eight stents constructed from the shape-memory nickel-titanium alloy nitinol were deployed by balloon expansion in the coronary arteries of 28 dogs and left in place for up to 6 months. Thirty minutes to 1 week after implantation, 70 stents were recovered by flushing the coronary arteries with 3 to 5 ml of 75 degrees C lactated Ringer solution, with collapse of the stent over a recovery catheter and subsequent withdrawal. RESULTS: All stents were successfully recovered and removed percutaneously. Mean vessel diameter after stenting was 12 +/- 6% (p < 0.05) greater than baseline diameter. Mean vessel diameter after stent removal remained enlarged (6 +/- 3%, p < 0.05). No angiographic or gross evidence of thrombosis, dissection, embolization, migration or spasm was associated with implantation or recovery. Microscopic examination revealed minor intimal injury in 40 segments (51%). Microscopic focal medial necrosis was associated with mural platelet-fibrin thrombus in 23 stented segments (29%) and media was interrupted in 7 (9%). CONCLUSIONS: This study demonstrates the feasibility of a new method of temporary stenting that uses the thermoelastic properties of nitinol to permit reliable recovery of the stent in normal canine coronary arteries.

A format for integrating the interpretation of exercise ejection fraction and wall motion and its application in identifying equivocal responses.

The conventional interpretation of ejection fraction change with exercise may be limited because it does not consider the rest value, define equivocal responses or integrate wall motion data reproducibly. Thus, a format was developed for combined interpretation of rest and exercise radionuclide ejection fraction and wall motion by reviewing the reported data for the exercise responses of patients without prior myocardial infarction. The ejection fraction data of 202 normal patients and of 259 patients with coronary artery disease were first fitted to beta distributions. The true positive and false positive rates for coronary disease for each combination of rest and exercise ejection fraction were then determined directly from these distributions. A given rest/exercise ejection fraction combination was "normal" if the false positive rate was greater than the true positive rate, or "abnormal" if the true positive rate was greater than the false positive rate, and "equivocal" when the rates were similar (within a 50% confidence interval). This analytic format, which predicted an inverse relation between rest ejection fraction and the change required with exercise, was then validated prospectively in 854 patients without myocardial infarction (557 with and 297 without angiographic coronary artery disease). Using the conventional criterion of an abnormal test result (less than 0.05 absolute rise in ejection fraction with exercise or a wall motion abnormality), sensitivity was 85 +/- 2% and specificity only 42 +/- 3%. The statistical format had a sensitivity of 70 +/- 2% and specificity of 70 +/- 3%, resulting in a twofold increase in information content. This format has at least two advantages over conventional interpretation: 1) it provides an explicit definition of equivocal responses; and 2) it reproducibly integrates discordant ejection fraction and wall motion responses and allows for the combined analysis of other nonscintigraphic observations, such as age and sex.

Laser ablation of human atherosclerotic plaque without adjacent tissue injury.

Seventy samples of human cadaver atherosclerotic aorta were irradiated in vitro using a 308 nm xenon chloride excimer laser. Energy per pulse, pulse duration and frequency were varied. For comparison, 60 segments were also irradiated with an argon ion and an Nd:YAG (neodymium:yttrium aluminum garnet) laser operated in the continuous mode. Tissue was fixed in formalin, sectioned and examined microscopically. The Nd:YAG and argon ion-irradiated tissue exhibited a central crater with irregular edges and concentric zones of thermal and blast injury. In contrast, the excimer laser-irradiated tissue had narrow deep incisions with minimal or no thermal injury. These preliminary experiments indicate that the excimer laser vaporizes tissue in a manner different from that of the continuous wave Nd:YAG or argon ion laser. The sharp incision margins and minimal damage to adjacent normal tissue suggest that the excimer laser is more desirable for general surgical and intravascular uses than are the conventionally used medical lasers.

In vivo ultrasound arterial recanalization of atherosclerotic total occlusions.

The purpose of this study was to assess the potential of intraarterial ultrasound for in vivo recanalization of atherosclerotic total occlusions. Ultrasound energy at a frequency of 20 kHz was applied with a prototype solid wire probe to 12 surgically implanted occluded human atherosclerotic arterial xenografts, 9 of which were calcified, as well as to the intimal surface of 12 normal canine arteries. In both the normal canine arteries and the atherosclerotic occluded xenografts, there was no angiographic evidence of vasospasm, thrombosis or arterial dissection. Eleven of the 12 atherosclerotic complete arterial occlusions were resistant to passage of a conventional guide wire or probe without ultrasound energy. However, the occlusions were recanalized after administration of 15 s to 4 min (mean 1.5 +/- 1.3 min) of intermittent ultrasound energy. After ultrasound, 8 of the 12 vessels underwent balloon angioplasty. Angiographic residual stenosis after ultrasound alone was 62 +/- 24% and after combined ultrasound and balloon angioplasty, 29 +/- 13%. Although routine angiography did not reveal arterial emboli, high resolution cut films did demonstrate a few distal nonocclusive thrombi of a size similar to that reported with other recanalization methods. Histologic studies demonstrated changes similar to those after balloon angioplasty, with focal cracking of the fibrotic and calcified plaque. The findings demonstrate that ultrasound energy applied through a catheter delivery system can be used in vivo to open completely obstructed atherosclerotic vessels. These studies suggest that it might be clinically feasible to use the ultrasound probe to create a lumen, allowing subsequent balloon dilation.

Should the intent of testing influence its interpretation?

A test is often interpreted as "normal" or "abnormal" by a single criterion, regardless of the intent of testing. The discriminate accuracy of this convention was critically analyzed using information content (I), likelihood ratio and the area under the receiver-operating characteristic curve. Three ejection fraction variables were assessed--ejection fraction at rest, exercise ejection fraction and the change in ejection fraction from rest to exercise--each relative to three intentional goals: diagnosis of coronary artery disease in 929 patients without previous myocardial infarction, prediction of multivessel disease in these same 929 patients and prediction of multivessel disease in 507 patients with previous myocardial infarction. The information content of exercise ejection fraction (IEX) was higher than for ejection fraction at rest (IR) or for the change from rest to exercise (IEX-R), and was relatively constant regardless of the goal of testing. In contrast, neither IR nor IEX-R was constant. IR was lowest for diagnosis of coronary artery disease, whereas IEX-R was highest for this same goal. These empiric observations are consistent with the quantitative relation predicted by information theory: IEX = IR + IEX-R. Thus, ejection fraction at rest has little discriminate value relative to the diagnosis of coronary artery disease, but does have value in evaluating the extent of disease in patients after myocardial infarction. Exercise ejection fraction and change in ejection fraction are nearly equally useful for purposes of diagnosis, whereas the former is most useful for functional evaluation in postinfarction patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Extent and severity of myocardial hypoperfusion as predictors of prognosis in patients with suspected coronary artery disease.

The ability of exercise-induced myocardial hypoperfusion on thallium scintigraphy to predict coronary events was assessed in 1,689 patients with symptoms suggestive of coronary artery disease but without prior myocardial infarction or coronary artery bypass surgery. A total of 74 patients had a coronary event in the year after testing (12 cardiac deaths, 20 nonfatal infarctions and 42 referrals for bypass surgery more than 60 days after testing). Stepwise logistic regression identified only three independent predictors: the number of myocardial regions with reversible hypoperfusion (an index of the extent of hypoperfusion), the maximal magnitude of hypoperfusion (an index of the severity of hypoperfusion) and the achieved heart rate (an index of exercise performance). Both extent and severity were exponentially correlated with event rate (r greater than 0.97 and p less than 0.01 for each), whereas achieved heart rate was linearly correlated with event rate (r = 0.79 and p less than 0.05). On the basis of these data, a prognostic model was defined that employs extent and severity as stress-dependent orthogonal variables. Using this model, the predicted coronary event rate ranged over two orders of magnitude--from a low of 0.4% in patients able to exercise adequately without developing severe and extensive hypoperfusion at a low heart rate (less than 85% of their maximal predicted heart rate). Extent and severity of myocardial hypoperfusion, therefore, are important independent variables of prognosis in patients with suspected coronary artery disease.